Role of Genetic Polymorphisms in the Development of Complications in Patients with Implanted Left Ventricular Assist Devices: HeartWare, HeartMate II, and HeartMate 3

Zhalbinova M.R. Rakhimova S.E. Kozhamkulov U.A. Akilzhanova G.A. Chinybayeva A.A. Akilzhanov K.R. Shaimardanov N.K. Kuanysheva A.G. Lee J.H. Kairov U.Y. Bekbossynova M.S. Akilzhanova A.R.
December 2023 Multidisciplinary Digital Publishing Institute (MDPI)

Journal of Clinical Medicine
2023 #12 Issue 23

Left ventricular assist device (LVAD) implantation is one of the mechanical circulatory support (MCS) treatments for advanced heart failure (HF) patients. MCS has emerged as a lifesaving therapy that improves patients’ quality of life. However, MCS remains limited by a paradoxical coagulopathy accompanied by thrombosis and bleeding. The mechanisms of MCS thrombosis are increasingly being defined, but MCS-related bleeding, which is related to shear-mediated alteration of platelet function, remains poorly understood. Complications might develop due to the high non-physiological shear stress in the device and as a consequence of individual variability in response to the antithrombotic therapy. Thromboelastography (TEG) and genotyping of gene polymorphisms that are involved in the coagulation cascade and in the metabolism of the antithrombotic therapy might be valuable sources of information for the reduction of complication development. The aim of the study was to identify genetic factors related to the development of device complications according to the implanted LVAD type. We compared the clinical and genetic data of HF patients (n = 98) with/without complications with three types of implanted devices: HeartWare HVAD (HW), HeartMate II (HMII), and HeartMate 3 (HM3). rs9923231 in VKORC1 (95%CI −6.28–0.22, p = 0.04) and rs5918 in ITGB3 genes (95%CI 0.003–4.36, p = 0.05) showed significant association with the TEG coagulation index parameter, which identified hyper- and hypo-coagulation states. The wild genotype of rs5918 in the ITGB3 gene prevailed in patients implanted with HM3 devices, which developed fewer complications than with HMII (p = 0.04). Individual genetic information could be useful in the management of patients with HF and the implantation of MCS to reduce the development of complications.

genotype , heart failure , left ventricular assist device (LVAD) , mechanical circulatory support (MCS) , polymorphism

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National Laboratory Astana, Nazarbayev University, Astana, 010000, Kazakhstan
Department of General Biology and Genomics, L. N. Gumilyov, Eurasian National University, Astana, 010000, Kazakhstan
Department of Medicine, Semey Medical University, Pavlodar Branch, Pavlodar, 140000, Kazakhstan
Republic Diagnostic Center, CF “University Medical Center”, Astana, 010000, Kazakhstan
Department of Medicine, Semey Medical University, Semey, 071400, Kazakhstan
Sergievsky Center, Taub Institute, Columbia University Medical Center, New York, 10032, NY, United States
National Research Cardiac Surgery Center, Astana, 010000, Kazakhstan
Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, 852-8523, Japan

National Laboratory Astana
Department of General Biology and Genomics
Department of Medicine
Republic Diagnostic Center
Department of Medicine
Sergievsky Center
National Research Cardiac Surgery Center
Atomic Bomb Disease Institute

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